Functionalized esters, such as ethyl 10-bromodecanoate, are used commonly in the synthesis of fine organic chemicals which, in turn, are used in pharmaceutical, flavor and fragrance, and agricultural products just to name a few. These compounds are especially useful as intermediates since the relatively-high reactivity of their functional group facilitates the compound's combination with other compounds to form complex esters. For example, ethyl 10-bromodecanoate is used as an intermediate in the production of drug carriers in the pharmaceutical field.
The traditional preparation of such functionalized esters, however, involves the consumption of expensive raw materials in reactions which are complex and difficult to control. Additionally, these reactions tend to have low yields and to result in the generation of unwanted by-products. For example, the conventional synthesis of ethyl 10-bromodecanoate involves a three-step process which is complex, costly and inefficient.
In the first step, 1,8-dibromooctane is alkylated using diethylmalonate, sodium ethoxide and ethanol to form 8-bromo octylmalonic acid diethylester. Besides being a relatively expensive, synthesized material, 1,8-dibromo octane is terminated in similar bromine functionality, which are equally as likely to react. Consequently, reactions involving just one of the bromine groups, like the alkylation reaction described above, tend to be difficult to control and result in poor selectivities. To some extent, the reaction of both bromo groups is unavoidable and the resulting compound, octanebismalonic acid tetraethylester, is similar enough to 8-bromo octylmalonic acid diethylester that separation between the two is difficult, thereby resulting in poor yields. Furthermore, the difficult separation of these compounds is particularly problematic since pharmaceutical applications mandate extremely high purity levels.
In the second step, 10-bromodecanoic acid is produced through the decarboxylation of the distilled 8-bromo octylmalonic acid diethylester produced in the first step. The timing of the termination of the decarboxylation is very critical, otherwise over-decarboxylation will occur to give low yields and impurities. Additionally, this step produces hazardous ethyl bromide as a byproduct which necessitates special handling.
In the third step, the desired product, ethyl 10-bromodecanoate, is produced through the esterification of 10-bromodecanoic acid in ethanol. The overall yield of this process is about 47%. In general, this process is costly, complex, inefficient, and produces hazardous waste.
Accordingly, there is a need for a process for preparing functionalized esters that uses relatively inexpensive starting materials and that involves reactions which are controlled readily to produce the desired product at high yields with minimal formation of hazardous byproducts. The present invention fulfills this need among others.